Summary

for females ages 18 years and up (full criteria)
at La Jolla, California and other locations
study started
estimated completion:

Description

Summary

This study evaluates the safety of abemaciclib in combination therapies (letrozole, anastrozole, tamoxifen, exemestane, exemestane plus everolimus, trastuzumab, LY3023414 plus fulvestrant, pertuzumab plus trastuzumab with loperamide) for breast cancer that has spread to other parts of the body.

Official Title

A Phase 1b Study of Abemaciclib in Combination With Therapies for Patients With Metastatic Breast Cancer

Keywords

Breast Neoplasms Letrozole Fulvestrant Exemestane Anastrozole Pertuzumab Trastuzumab Everolimus Sirolimus Tamoxifen Estradiol Loperamide Antidiarrheals LY2835219 LY3023414 Endocrine therapy LY2835219 + Letrozole LY2835219 + Anastrozole LY2835219 + Tamoxifen LY2835219 + Exemestane LY2835219 + Exemestane + Everolimus Dose Escalation LY2835219 + Exemestane + Everolimus Dose Expansion LY2835219+ Trastuzumab Dose Escalation LY2835219+ Trastuzumab Dose Expansion LY3023414 + LY2835219 + Fulvestrant Dose Escalation LY3023414 + LY2835219 + Fulvestrant Dose Expansion LY2835219 +Trastuzumab +Pertuzumab +Loperamide Dose Escalation LY2835219 +Trastuzumab + Pertuzumab +Loperamide Dose Expansion LY2835219 + Endocrine Therapy

Eligibility

You can join if…

Open to females ages 18 years and up

  • Have a diagnosis of hormone receptor positive (HR+), human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer for Parts A to E, G, and I.
  • Have a diagnosis of human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer for Parts F and H.
  • For Part A (LY2835219 + letrozole): Except for ongoing therapy with letrozole, the participant must not have received prior systemic endocrine therapy for metastatic disease.
  • For Part B (LY2835219 + anastrozole): Except for ongoing therapy with anastrozole, the participant must not have received prior systemic endocrine therapy for metastatic disease.
  • For Part C (LY2835219 + tamoxifen): The participant may have received prior systemic endocrine therapy for metastatic disease and may be receiving ongoing therapy with tamoxifen.
  • For Part D (LY2835219 + exemestane): The participant must have received prior systemic endocrine therapy with at least one nonsteroidal aromatase inhibitor (anastrozole,letrozole) for metastatic disease and may be receiving ongoing therapy with exemestane.
  • For Part E (LY2835219 + exemestane + everolimus): The participant must have received prior systemic endocrine therapy with at least one nonsteroidal aromatase inhibitor(anastrozole, letrozole) for metastatic disease and may be receiving ongoing therapy with either exemestane or exemestane + everolimus.
  • For Part F (LY2835219 + trastuzumab):The participant must have received at least 1 chemotherapy regimen for metastatic disease and may be receiving ongoing therapy with trastuzumab. The participant must have an estimated left ventricular ejection fraction within the normal range by either echocardiogram or multigated acquisition (MUGA) scan
  • For Part G (abemaciclib + LY3023414 + fulvestrant): The participant may have received prior systemic endocrine therapy with at least one nonsteroidal aromatase inhibitor(anastrozole, letrozole) for metastatic disease.
  • For Part H: (abemaciclib + trastuzumab + pertuzumab): The participant must have received at least 1 chemotherapy regimen for metastatic disease. The participant may be receiving ongoing therapy with trastuzumab and/or pertuzumab at the time of study entry. The participant must have an estimated left ventricular ejection fraction(LVEF) within the normal range by either echocardiogram or multigated acquisition(MUGA) scan.
  • For Part I (abemaciclib + endocrine therapy): The participant must have demonstrated evidence of disease progression on a Cyclin Dependent Kinase 4 (CDK4) and Cyclin Dependent Kinase 6 (CDK6) inhibitor (either palbociclib or ribociclib) plus endocrine therapy for advanced or metastatic disease as the most recent therapy immediately preceding study entry. The participant should remain on the current endocrine therapy while receiving abemaciclib.
  • For Parts A, B, C, D, E, and F: Have either measureable disease or nonmeasureable but evaluable bone disease as defined by the Response Evaluation Criteria in Solid Tumors(RECIST 1.1)
  • For Part G, H, and I: Have measureable disease as defined by RECIST 1.1.
  • For all Parts except Part F and H: Participants must have either post-menopausal status or pre-menopausal status if continuing or beginning ovarian suppression with a luteinizing hormone-releasing hormone (LHRH) agonist such as goserelin.
  • Parts H, and I: Must be able and willing to undergo mandatory tumor biopsies prior to study treatment and at the time of discontinuation from study treatment.
  • Have adequate organ function, including:
  • Hematologic: Absolute neutrophil count (ANC) ≥1.5 x 109/liter (L), platelets ≥100 x 109/L, and hemoglobin ≥ 8 gram/deciliter (g/dL).

  • Hepatic: Bilirubin ≤1.5 times upper limits of normal (ULN), alanine aminotransferase (ALT) ≤ 3.0 times ULN.
  • Renal: Serum creatinine ≤ 1.5 times ULN.
  • Have a performance status of ≤1 on the Eastern Cooperative Oncology Group (ECOG)scale.
  • Have discontinued all previous therapies for breast cancer (including chemotherapy,radiotherapy, immunotherapy, and investigational therapy), except for ongoing corresponding combination therapy, for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug(s), and recovered from the acute effects of therapy (until the toxicity resolves to either baseline or at least Grade 1) except for residual alopecia or peripheral neuropathy. For Part F and H: concurrent treatment with trastuzumab emtansine (T-DM1) is not allowed.

You CAN'T join if...

  • Have metastatic breast cancer with severe organ dysfunction as assessed by symptoms and signs, laboratory studies, and rapid progression of the disease.
  • Have brain metastasis without prior radiotherapy.
  • For Parts A, B, C, D, E, G and I: Have received prior systemic chemotherapy for metastatic disease. However, the participant may have received prior systemic chemotherapy in the neoadjuvant or adjuvant setting.
  • For Parts A, B, C, D, E, F, H: Have received prior therapy with a CDK4/6 inhibitor,

Part G: Have received prior therapy with fulvestrant or any PI3K and/or mTOR inhibitor(including LY3023414); Part I: Have received prior treatment with abemaciclib in any setting.

  • Have serious preexisting medical conditions that, in the judgment of the investigator,would preclude participation in this study (for example, history of major surgical resection involving the stomach or small bowel).
  • Have central nervous system (CNS) metastasis with either radiotherapy or development of neurological changes ≤14 days prior to receiving study treatment. Participants may be receiving a stable dose of corticosteroids. Screening of asymptomatic participants without history of CNS metastasis is not required. Untreated CNS metastases are not permitted.
  • For Parts F and H: Cardiac disease including myocardial infarction within 6 months,unstable angina, or New York Heart Association (NYHA) Grade II or greater functional impairment.
  • For Part G: Have type 1 diabetes mellitus or a history of gestational diabetes mellitus. Participants with a type 2 diabetes mellitus are eligible if adequate control of blood glucose level is obtained with oral therapy as documented by Hemoglobin A1c <7%.
  • For Part G: Have a baseline electrocardiogram (obtained from Day -14 to Day -1) with any of the following abnormal findings: ventricular arrhythmia, evidence of acute myocardial ischemia, heart block (of any degree), or QTc prolongation (defined as QTcB≥450 milliseconds).

Locations

  • University of California - San Diego accepting new patients
    La Jolla California 92037-0845 United States
  • Providence Cancer Center Oncology Hematology Care accepting new patients
    Portland Oregon 97213 United States
  • South Texas Accelerated Research Therapeutics, LLC accepting new patients
    San Antonio Texas 78229-3307 United States
  • University of Oklahoma Health Sciences Center accepting new patients
    Oklahoma City Oklahoma 73104 United States
  • Texas Oncology-Baylor Charles A. Sammons Cancer Center in progress, not accepting new patients
    Dallas Texas 75246 United States
  • SMO US Oncology in progress, not accepting new patients
    The Woodlands Texas 77380 United States
  • Highlands Oncology Group accepting new patients
    Fayetteville Arkansas 72703 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Eli Lilly and Company
Links
Click here for more information about this study: A Study of Abemaciclib (LY2835219) in Combination With Other Therapies in Participants With Breast Cancer That Has Spread
ID
NCT02057133
Phase
Phase 1
Study Type
Interventional
Last Updated
May 22, 2018